Abstract Type A and B Influenza viruses cause severe seasonal epidemics and less frequent but more deadly pandemic infections. Vaccination provides the best protection, although serious problems are confronting the global Influenza market. Virus diversity and mutation rates necessitate the annual production of hundreds of millions of vaccines using antiquated egg-based technologies. Compounding this is the risk of choosing the wrong vaccine strain, which leads to sharp drops in efficacy and increased infection rates. New transformational technologies are needed to combat Influenza. The best solution is a universal vaccine that will establish long- term immunity against all genetic strains. This can only be accomplished by constructing vaccines around highly conserved protein sequences common to all viruses. Importantly, these antigens are known and numerous studies indicate that vaccines targeting linear epitopes within 4 viral proteins can be used to induce protective antibodies against both Type A and Type B viruses. TRIA Bioscience is developing a self-assembling peptide nanoparticle vaccine platform that incorporates these and similar linear B cell epitopes directly into synthetic peptides capable of stimulating significant functional antibody responses. The ease of production and formulation of such peptides makes this an ideal technology for mass production. We propose to build a multivalent universal Influenza vaccine that targets these highly conserved epitopes and confers long-lived immunity against multiple Influenza classes and strains. Mice will be immunized with individual peptides to confirm that each epitope induces an antiviral antibody response. The relative potency of each vaccine will be evaluated in mouse challenge studies and multivalent formulations will tested for improved protection against Influenza A and B viruses.